Process of making acetylacetylamino acetone and the product thereof



Patented Dec. 29, 1942 t 2 305 755 UNITED -OFFICE I r nooss s or is'mxmo Act-imam smomc e'rons mm'ruemonucr This invention relates to acetylacetylaminof. acetones, and processes or preparins'tthe same;.

I have discovered thatthevmethylenesgrou :1. of acetyl-acetone; substituted 1 acetylacetone; ma-: 2 ionic esters, cyanoacetic. esters x etcsiwill react with compounds which containc'ab'doubl 'mond; oxygen, or which are capable of forming a double bond oxygen, such as ortho-esters and nitrous acid. to introduce an alkoxymethyleneor an nitroso group into the 'moleculezjfl'lienlkoiry l methylene group thus introduced-may reacted with ammonia; an amine organ Jammehavmgs least one hydrogen, to i'o'r'm ftheQcorr p aminomethylene or amidomethylene group;

I have also discovered that" the f aminom'ethy ene, amidomethylene and'isonitroso fithejlat' in the presence of an agent 'whichfjcanfstahiliz the amino groupps'uch as an acid' ah hydrid an acid, etc.) derivatives may 'bejhydrogenate to form the corresponding aminomethylyam o- 1 methyl, amine salts or "facylarninq'" derive;tiv These new compounds :inay be illustrated by carbamoacetic esters et g: I

The following exampl illustrate methods of nY-QPEEQ; D1

general formula:

wherein R1 is a; member Selectedfromthe group consisting of alkoxyacylgacyl, 'carbalko iygq nd alk xy R s ct 1m vt gr up, B9. sisting of alkoxy, and: hydrogem fls is selecte Irom the group consisting'foralkoxy, acylamin alkyl and 'acylamino,t and;Wh m nd 3 together may represent a memher selected the group consisting of alkoxymethyl "a methylene, acylaminomethylenm alkosya H koxymethylene, mine; alkoxyalkylacylamin methylene, isonitroso; Rit is' 'af, member; se; lected from the group .cbnsisitihg ofv acyl alkox acyLaIkosy, and cyanogen.

a The above compoundsmay-he obtained cc snem s: e I

.1 v d: .Pd; 5 2 k -@93 h 13E JQQfliDS'r: point up to 153 C 4 mm. is removed and 35 refractionated. 65 g Rim N the mother liquors, a further quantity bf it'h (IL-5C .7 product is obtained. total yield of l-ethoxy- It 5 3-aminomethylene p ,4-dione is 1 t'f' 'fiiirified the refrigerator.

1.8 grams of pale brown neegrams benzamide, and the mixture heated at 150 mixture allowed to stand for 8 hours at room tem erature. Water is added, the mixture extracted with ether, the ether is thoroughly washed with water. and dried over sodium sulfate. The product obtained on removal of the ether is dissolved in 80% alcohol, and on coolins. 1.1 grams of needles are obtained. After recrystallization from alcohol, the l-ethoxy- 8 benzoylaminomethylene pentane-2,4-dione is obtained, having a melting point of 95-96 C.

1.63 grams of 1-ethoxy-8-benzoylaminomethylene pentane-2.4-dlone are dissolved in '15 cc. ethyl alcohol, and hydrogenatedinthe presence of 0.1 gram platinum oxide. 136 cc. of hydrogen are taken up in 6 minutes (theory 132 0a.). The

catalyst is removed by filtration and the solvent evaporated under reduced pressure. The l-ethcxy-s-benzoylaminomethyl pentane-2,4-.dione is a viscous pale brown oil, which upon crystallization from ether and recrystallization from ethyl acetate, gives colorless fine needles, melting point 89-90 C. Yield 1.65 grams.

Example 2 2.2 grams of 3-benaoylaminomethylene pentane-2,4-dione 'are dissolved in 100 cc. ethyl alcohol and hydrosenated in the presence of 0.1 gram of a platinum catalyst. The theoretical amount of hydrogen is taken up rapidly. After removal of the catalyst by filtration, the filtrate is concentrated under reduced pressure to a volume of 5 cc. 9n cooling, the S-benzoylaminomethyl pentane-2,4-dione crystallizes as colorless needles, and after recrystallization with alcohol, melts at 87-68 C. The yield is 1.65 grams.

Example 3 2 grams of ethyl-a-benzoylaminomethyleneacetoacetote are dissolved in 150 cc. of ethyl alcohol and hydrogenated in thepresence of 0.1 gram of a platinum catalyst. The catalyst is removed by filtration and the solvent removed by evaporation under reduced pressure. The ethyl-a-benzoylaminomethyl acetoacetate is a faintly yellow oil which crystallizes on standing. After recrystallization from ether-petroleum ether, it is obtained as colorless needles, melting point 56 0. Yield 1.90 grams.

Example 4 26 grams of ethyl-gamma-ethoxy acetoacetate, 22.1 grams of ethyl orthoformate, and 30.5 grams of acetic anhydride are refiuxed for 40 minutes. The reaction mixture is then distilled until the temperature reaches 122' C. The residue is distilled through a fractionating column at 8 mm. up to 165 C. and then refractionated at 5 mm. The fraction boiling at 146-52 C. at 5 mm. crystallizes on standing at 0 C. After separating from a little oily material and recrystallizing from petroleum ether, the ethyl-a-ethoxymethylene-gamma-ethoxy acetoacetate is obtained as colorless fine long needles, melting point 57-58 C. The oily material on cooling gives further crystals. Total yield 19.7 grams.

C. for 60 minutes. After cooling. alcohol is added and the product is obtained as pale brown plates on standing at 0' C. The yield of ethyl-a-benzoylaminomethylene-gamma-ethoxy acetoacetate is 8 grams. On recrystallization from alcohol it melts at 96-98 C.

2 .grams of ethyl-a-benzoylaminomethylenegamma-ethoxy acetoacetate are dissolved in 150 cc. alcohol and hydrogenated in the preemce of 0.1 gram of a platinum catalyst. The catalyst is removed by filtration and the solvent removed by concentration under reduced pressure. The ethyl-c-benzoylan inomethyl-gamma-ethoxy acetoacetate obtained is distilled and obtained as an almost colorless oil.

Example 5 aceto iminoethyl ether hydrochloride. The

crystals are dried and freed from hydrogen .chloride in vacuo over soda lime for 24 hours. 'The yield is 220 to 260 grams.

849 grams of finely ground methoxy-aceto-imino-ethyl-ether hydrochloride are suspended in 2300 cc. of absolute alcohol and shaken at room temperature for two weeks. The solids are then removed by filtration and the mother liquor allowed to stand in contact with 10 grams of freshly ignited potassium carbonate over night to remove traces of acid. The filtrate from the potassium carbonate is fractionated at 15 mm. pressure; the first fraction boiling up to 35 C. consists mainly-of alcohol, th second fraction boiling up to 70 C. consists mainly of ethyl-methoxyacetate. The fraction boiling at 7045 C. is the crude methoxy-ethyl-ortho-acetate. This fraction is kept at 0 C. for 16 hours, and the small amount of methoxy-acetamid which crystallizes out is filtered oil'. .The filtrate is refractionated at ordinary pressure and the fraction boiling at -l'75 C. is again fractionated. The methoxy-ethyl-ortho-acetate thus obtained boils at 173-175 C. The yield is 300 grams. The

mixture of ammonium chloride and unchanged j imino ether hydrochloride, which is filtered of! after shaking, is again shaken with the recov ered alcohol, the volume being made up with fresh alcohol. By this means a further quantity of the ortho-acetate is obtained.

A mixture of 96 grams of methoxy-ethyl-orthoacetate, 65 grams acetoacetic ester, and 62 grams of freshly distilled acetic anhydride is refluxed pentene-4-one.

Example 6 A mixture of 113 grams cyanacetic ester, 192 grams ethyl-methoxy-ortho-acetate and 204 grams acetic anhydride are refluxed for one hour,

' and the pale yellow mixture is then distilled up to 115 C. The residue is again refluxed for an hour and again distilled till the vapour temperature reaches 115 C. The residue is distilled at 15 mm. till the vapour temperature reaches 106 C. The residue gives as a main fraction a very faintly yellow liquid, boiling point 129-130 C. at 0.6 mm. Yield 70 grams. n cooling at 0 C., the product crystallizes and on recrystallization from ether-petroleum ether, ethyia-cyanop-ethoxy-gamma-methoxy crotonate is obtained as colorless square plates, melting point 42-44" C. Upon treating the latter compound with benzamide, a-cyano s benzoylamino gammamethoxy crotonate is obtained.

Example 7 50 grams of acetylacetone are mixed with 500 cc. of 7% sulfuric acid, and the mixture is cooled to 0 C. 35 grams of sodium nitrite dissolved in 150 cc. H2O are slowly dropped in with stirring. After the addition is complete, the mixture is stirred for an additional 15 minutes and then extracted with ether. The ether is dried with tion takes place. It is taken up in the minimum amount of ether, and petroleum ether is care- 1 .fully added to the cooled solution until turbidity sodium sulfate after washing with water. The

ether is removed and the syr py residue crystallizes on scratching. The isonitroso-acetylacetone is dried and freed from nitrous fumes in vacuum. Melting point 75 C.

2.15 grams of isonitroso-acetylacetone are dissolved in 50 cc. of freshly distilled acetic anhydride, and hydrogenated in the presence of Adam's platinum catalyst at ordinary pressure. The theoretical amount of hydrogen (800 cc.) is taken up in 20 minutes, and the reaction is stopped. The catalyst is filtered oil, the solvent removed in vacuum, and the 3-(acetylamino)- 'acetylacetone crystallizes in colorless prisms;

yield 2.2 grams. After recrystallization from ethyl acetate, it has a melting point of 93-94 C.

E's-ample 8 appears. Upon vigorous scratching and cooling to 10 C., isonitroso-ethoxy-acetylacetone crystallizes in colorless thin plates. It is filtered, and washed with petroleum ether-ether (30:70). Yield, 18 grams.

After recrystallization from ether-petroleum ether, the thin colorless pla s have a melting point 01. 93-95 C.

The mother liquor on evaporation gives 9. amp which crystallizes on standing, and on treatment with ether-petroleum ether, gives a further 8 grams of crystalline material.

The above mother liquor on evaporation again crystallizes, and after filtering from syrupy material, gives a further 25 grams of isonitrosoethoxy-acetylaoetone.

By repeating these procedures, further pure material can be obtained.

10 grams of isonitroso-ethoxy-acetylacetone are dissolved in 225 cc. of freshly distilled acetic anhydride, and hydrogenated at ordinary pressure in the presence of 0.3 gram of platinum oxide catalyst. The theoretical amount of hydrogen is taken up rapidly, and the hydrogenation is stopped. After removal of the catalyst, the acetic anhydride is removed in vacuum at a low temperature. The residue (12 grams) is a pale yellow oil. All attempts to crystallize this material fail, although a small amount of crystalline by-product is obtained (0.3 gram, M. P. 101-102 C.) from ether-petroleum ether, which analyzes for CnHmOsN. The syrupy 3-(acetylamino) ethoxy-acetylacetone cannot be distilled at 0.3 mm. without extensive decomposition.

Modifications may be made in ca yin out the present invention without departing from the spirit and scope thereof, and I am to be limited only by the appended claims.

I claim:

1. l-acetyl-l-acetylamino acetone.

2. l-ethoxyacetyl-l-acetylamino acetone.

3. The process comprising treating ethoxyacetyl-acetone with nitrous acid to form isonitroso-ethoxy-acetylacetone, and hydrogenating the latter compound in the presence-of acetic anhydride.

4. The process comprising treating ethoxyacetylacetone with nitrous acid to form lsonitroso-ethoxy-acetylacetone.

5. A compound selected from the group consisting of l-acetyl-l-acetylamino acetone and l-ethoxyacetyl-l-acetylamino acetone.

ERIC T. S'I'l'LLER. 

